Quality of Life and Exercise Capacity in Early Stage and Subclinical Hypertrophic Cardiomyopathy: A Secondary Analysis of the VANISH Trial.

BACKGROUND: The health-related quality of life (HRQOL) and cardiopulmonary exercise testing (CPET) performance of individuals with subclinical and early stage hypertrophic cardiomyopathy (HCM) have not been systematically studied. Improved understanding will inform the natural history of HCM and factors influencing well-being. METHODS: VANISH trial (Valsartan for Attenuating Disease Evolution in Early Sarcomeric HCM) participants with early stage sarcomeric HCM (primary analysis cohort) and subclinical HCM (sarcomere variant without left ventricular hypertrophy comprising the exploratory cohort) who completed baseline and year 2 HRQOL assessment via the pediatric quality of life inventory and CPET were studied. Metrics correlating with baseline HRQOL and CPET performance were identified. The impact of valsartan treatment on these measures was analyzed in the early stage cohort. RESULTS: Two hundred participants were included: 166 with early stage HCM (mean age, 23±10 years; 40% female; 97% White; and 92% New York Heart Association class I) and 34 subclinical sarcomere variant carriers (mean age, 16±5 years; 50% female; and 100% White). Baseline HRQOL was good in both cohorts, although slightly better in subclinical HCM (composite pediatric quality of life score 84.6±10.6 versus 90.2±9.8; P=0.005). Both cohorts demonstrated mildly reduced functional status (mean percent predicted peak oxygen uptake 73±16 versus 78±12 mL/kg per minute; P=0.18). Percent predicted peak oxygen uptake and peak oxygen pulse correlated with HRQOL. Valsartan improved physical HRQOL in early stage HCM (adjusted mean change in pediatric quality of life score +4.1 versus placebo; P=0.01) but did not significantly impact CPET performance. CONCLUSIONS: Functional capacity can be impaired in young, healthy people with early stage HCM, despite New York Heart Association class I status and good HRQOL. Peak oxygen uptake was similarly decreased in subclinical HCM despite normal left ventricular wall thickness and excellent HRQOL. Valsartan improved physical pediatric quality of life scores but did not significantly impact CPET performance. Further studies are needed for validation and to understand how to improve patient experience. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01912534.

Safety of Bimekizumab for Plaque Psoriasis: An Expert Consensus Panel.

BACKGROUND: Plaque psoriasis is a chronic, relapsing systemic illness that has a significant effect on quality of life. Bimekizumab is the first monoclonal antibody to target both interleukin (IL)-17A and IL-17F, and recently received Food and Drug Administration (FDA) approval for moderate to severe plaque psoriasis. Guidance is necessary regarding the safety of bimekizumab. METHODS: A comprehensive literature search of PubMed, Scopus, and Google Scholar was completed for English-language original research articles on the safety of bimekizumab for moderate to severe psoriasis. A panel of 9 dermatologists and 1 rheumatologist with significant expertise in the treatment of psoriasis gathered to review the articles and create consensus statements on this new medication. A modified Delphi process was used to approve each statement, and strength of recommendation was assigned using the Strength of Recommendation Taxonomy criteria. RESULTS: The literature search produced 110 articles that met the criteria. A thorough screening of the studies for relevance to the research question resulted in 15 articles. These were distributed to all panelists for review prior to a roundtable discussion. The panel unanimously voted to adopt 5 consensus statements and recommendations, all of which were given a strength of "A". CONCLUSION: Bimekizumab has a safety profile consistent with other biologics, except for a higher risk of oral candidiasis. Its hepatic safety profile is comparable with other currently FDA-approved biologics for plaque psoriasis. In addition, the data do not support an association of bimekizumab with suicide, and the incidence of inflammatory bowel disease is not greater than the incidence of other IL-17 blockers. J Drugs Dermatol. 2024;23(8):592-599. doi:10.36849/JDD.8246.

Integrating Health Informatics into Pre-Registration Nursing Education: Insights from a Participatory Workshop.

The implementation of health informatics in pre-registration health professional degrees faces persistent challenges, including curriculum overload, educator workforce capability gaps, and financial constraints. Despite these barriers, reports of successful implementation of health informatics pre-registration nursing programs exist. A virtual workshop was held during thein 15th International Nursing Informatics Conference in 2021 with the aim to explore successful implementation strategies for incorporating health informatics into the nursing curriculum to meet the accreditation standards. This paper reports recommendations from the workshop emphasising the importance academic-clinical partnerships to develop innovative approaches to enhance theof capacity of academic teams and access to contemporary point of care digital technologies that reflect applications of health informatics in interdisciplinary clinical settings.

Mapping Trust in Nurses with Dimensions of Trustworthy Artificial Intelligence: A Scoping Review.

This scoping review examines the concept of trust in nursing and its potential application in developing trustworthy Artificial Intelligence (AI) for healthcare. Recognizing nurses as highly trusted professionals, the study explores how attributes contributing to trust in nursing can inform AI development. Following the Joanna Briggs Institute framework, the review synthesizes literature on patients' perceptions of nurses' trustworthiness and compares these with desired qualities in trustworthy AI. Preliminary findings suggest that nursing's trust-inducing actions could offer valuable insights for implementing trust-enhancing features in AI. This approach aims to bring innovative insights into the nature of trust and contribute to creative solutions to develop trustworthy AI in healthcare. By aligning AI development with principles of trust observed in nursing, the review proposes novel strategies for creating more ethical and accepted AI systems in healthcare settings.

Resource Utilization and Costs Associated With Cardiogenic Shock Complicating Myocardial Infarction: A Population-Based Cohort Study.

Background: Cardiogenic shock due to acute myocardial infarction (AMI-CS) is associated with significant short- and long-term morbidity and mortality. Despite this, little is known about associated cost. Objectives: The purpose of this study was to evaluate the health care costs and resource use associated with AMI-CS using administrative data from the province of Ontario, Canada. Methods: This was a retrospective cohort study of adult patients with AMI-CS from April 2009 to March 2019. One-year costs following index admission were reported at an individual level. We used generalized linear models to identify factors associated with increased cost. We stratified patients by revascularization strategy to compare cost in each group and examined total cost at a patient level per individual fiscal year. Results: We included 9,789 consecutive patients with AMI-CS across 135 centers in Ontario (mean age 70.5 years; 67.7% male). Mortality in-hospital was 30.2%, and mortality at 2 years was 45.9%. The median inpatient cost per patient was $23,912 (IQR: $12,234-$41,833) with a median total 1-year cost of $37,913 (IQR: $20,113-$66,582). The median 1-year cost was $17,730 (IQR: $9,323-$38,379) for those who died in hospital, and $45,713 (IQR: $29,688-$77,683) for those surviving to discharge, with $12,719 (IQR: $4,262-$35,275) occurring after discharge. Patients who received coronary artery bypass grafting incurred the highest cost among revascularization groups. No significant differences were observed in cost per fiscal year from 2009 to 2019. Conclusions: AMI-CS is associated with significant health care costs, both during the index hospitalization and following discharge. To optimize cost-effectiveness, future therapies should aim to reduce disability in addition to improving mortality.

Targeted Mass Spectrometry for Quantification of Receptor Tyrosine Kinase Signaling.

Targeted proteomics enables sensitive and specific quantification of proteins and post-translational modifications. By coupling peptide immunoaffinity enrichment with targeted mass spectrometry, we have developed the methodology for multiplexed quantification of proteins and phosphosites involved in the RAS/MAPK signaling network. The method uses anti-peptide antibodies to enrich analytes and heavy stable isotope-labeled internal standards, spiked in at known concentrations. The enriched peptides are directly measured by multiple-reaction monitoring (MRM), a well-characterized quantitative mass spectrometry-based method. The analyte (light) peptide response is measured relative to the heavy standard. The method described provides quantitative measurements of phospho-signaling and is generally applicable to other phosphopeptides and sample types.

How c-di-GMP controls progression through the Streptomyces life cycle.

Members of the antibiotic-producing bacterial genus Streptomyces undergo a complex developmental life cycle that culminates in the production of spores. Central to control of this cell differentiation process is signaling through the second messenger 3', 5'-cyclic diguanylic acid (c-di-GMP). So far, three proteins that are directly controlled by c-di-GMP in Streptomyces have been functionally and structurally characterized: the key developmental regulators BldD and σWhiG, and the glycogen-degrading enzyme GlgX. c-di-GMP signals through BldD and σWhiG, respectively, to control the two most dramatic transitions of the Streptomyces life cycle, the formation of the reproductive aerial hyphae and their differentiation into spore chains. Later in development, c-di-GMP activates GlgX-mediated degradation of glycogen, releasing stored carbon for spore maturation.

Predictors of long-term progression-free survival in patients with ovarian cancer treated with niraparib in the PRIMA/ENGOT-OV26/GOG-3012 study.

OBJECTIVE: To identify characteristics associated with long-term progression-free survival (≥2 years) in patients with advanced ovarian cancer treated with niraparib first-line maintenance therapy in the phase III PRIMA/ENGOT-OV26/GOG-3012 study. METHODS: In this post hoc analysis of PRIMA, patients randomized to niraparib were grouped based on investigator-assessed progression-free survival (progressive disease/censoring <2 years or ≥2 years after randomization). Variables assessed for predictive value were Eastern Cooperative Oncology Group performance status, International Federation of Gynecology and Obstetrics (FIGO) stage at diagnosis, clinical response to platinum-based chemotherapy, number of prior chemotherapy cycles, primary tumor location, body mass index, categorical age, debulking surgery type, number of baseline target lesions, number of baseline non-target lesions, BRCA/homologous recombination-deficiency status, residual disease status, and duration from end of chemotherapy to randomization. Logistic regression modeling using backward elimination (significance level=0.15) identified covariates associated with long-term progression-free survival (clinical cut-off date November 17, 2021). RESULTS: Of 487 patients randomized to niraparib, 152 (31%) had progressive disease/censoring ≥2 years after randomization. Multivariable logistic regression modeling using backward elimination identified BRCA1/2 mutation/homologous recombination deficiency status (p<0.0001), FIGO stage (p=0.041), primary tumor location (p=0.095), and number of baseline non-target lesions (p=0.0001) to be associated with long-term progression-free survival. Patients significantly more likely to achieve progression-free survival of ≥2 years in the final model were those with BRCA1- and BRCA2-mutated/homologous recombination-deficient tumors or BRCA wild-type/not determined/homologous recombination-deficient tumors (vs BRCA wild-type/homologous recombination-proficient/not determined tumors), FIGO stage III (vs IV), and 0 or 1 baseline non-target lesions (vs ≥2 baseline non-target lesions). CONCLUSIONS: The hypothesis-generating results of this analysis suggest that BRCA1/2 mutation/homologous recombination-deficiency status, FIGO stage, and number of baseline non-target lesions may predict progression-free survival of ≥2 years in patients with advanced ovarian cancer receiving niraparib first-line maintenance therapy. TRIAL REGISTRATION NUMBER: NCT02655016.

The Impact of Next-Generation Sequencing Added to Multiplex PCR on Antibiotic Stewardship in Critically Ill Patients with Suspected Pneumonia.

INTRODUCTION: In patients with suspected pneumonia who are tested with respiratory culture and multiplex PCR, the potential added benefit of next-generation sequencing technologies is unknown. METHODS: This was a single-center, retrospective study in which residual bronchoalveolar lavage (BAL) specimens were retrieved from hospitalized patients. We compared its research-use-only Respiratory Pathogen Illumina Panel (RPIP) results to culture and BioFire® FilmArray Pneumonia Panel (BioFire® PN) results from critically ill patients. RESULTS: In total, 47 BAL specimens from 47 unique patients were included. All BAL samples were tested with culture and multiplex PCR. In total, 38 of the 47 BALs were consistent with a clinical picture of pneumonia per chart review. Additional testing of the 38 samples with the RPIP identified a new bacterium in 20 patients, a new virus in 4 patients, a new bacterium plus virus in 4 patients, and no additional organisms in 10 patients. In 17 (44.5%) of these patients, the RPIP results could have indicated an antibiotic addition. Compared with cultures, the RPIP had an overall sensitivity of 64% and specificity of 98%, with a 0% sensitivity for fungus and 14% sensitivity for mycobacteria. Compared with BioFire® PN, the RPIP was 70% sensitive and 99% specific, with a 74% sensitivity for bacteria and 33% sensitivity for viruses. The RPIP was 29% more sensitive for HAP/VAP bacterial targets compared with CAP. CONCLUSIONS: Emerging NGS technologies such as the RPIP may have a role in identifying the etiology of pneumonia, even when patients have BAL culture and multiplex PCR results available. Similar to prior studies evaluating RPIP, our study showed this platform lacked sensitivity when compared with cultures, particularly for fungi and mycobacteria. However, the high specificity of the test can be leveraged when clinicians are seeking to rule out certain infections.

Connected communities: Perceived neighborhood social cohesion during adolescence and subsequent health and well-being in young adulthood-An outcome-wide longitudinal approach.

Does higher perceived neighborhood social cohesion in adolescence lead to better health and well-being 10-12 years later? We evaluated this question using data from a large, prospective, and nationally representative sample of US adolescents (Add Health; N = 10,963), and an outcome-wide approach. Across 38 outcomes, perceived neighborhood social cohesion was associated with some: mental health outcomes (i.e., depressive symptoms, suicidal ideation, perceived stress), psychological well-being outcomes (i.e., happiness, optimism), social outcomes (i.e., loneliness, romantic relationship quality, satisfaction with parenting), and civic/prosocial outcomes (i.e., volunteering). However, it was not associated with health behaviors nor physical health outcomes. These results were maintained after robust control for a wide range of potential confounders.

A methodological pipeline for the preclinical evaluation of novel topical agents for the treatment of CRS.

KEY POINTS: Novel topical therapeutics require extensive pre-clinical testing to assess efficacy and safety. Antibiofilm or immunosuppressant agents can utilize ex vivo models to measure ciliotoxicity. Agents that are found to be effective and non-toxic ex vivo warrant further investigation in vivo.

Northwestern University resource and education development initiatives to advance collaborative artificial intelligence across the learning health system.

Introduction: The rapid development of artificial intelligence (AI) in healthcare has exposed the unmet need for growing a multidisciplinary workforce that can collaborate effectively in the learning health systems. Maximizing the synergy among multiple teams is critical for Collaborative AI in Healthcare. Methods: We have developed a series of data, tools, and educational resources for cultivating the next generation of multidisciplinary workforce for Collaborative AI in Healthcare. We built bulk-natural language processing pipelines to extract structured information from clinical notes and stored them in common data models. We developed multimodal AI/machine learning (ML) tools and tutorials to enrich the toolbox of the multidisciplinary workforce to analyze multimodal healthcare data. We have created a fertile ground to cross-pollinate clinicians and AI scientists and train the next generation of AI health workforce to collaborate effectively. Results: Our work has democratized access to unstructured health information, AI/ML tools and resources for healthcare, and collaborative education resources. From 2017 to 2022, this has enabled studies in multiple clinical specialties resulting in 68 peer-reviewed publications. In 2022, our cross-discipline efforts converged and institutionalized into the Center for Collaborative AI in Healthcare. Conclusions: Our Collaborative AI in Healthcare initiatives has created valuable educational and practical resources. They have enabled more clinicians, scientists, and hospital administrators to successfully apply AI methods in their daily research and practice, develop closer collaborations, and advanced the institution-level learning health system.

Does Soaking Fresh Frozen Costal Cartilage in an Antibiotic Solution Reduce Postoperative Infection in Rhinoplasty?

Background: Fresh frozen costal cartilage (FFCC), from the Musculoskeletal Transplant Foundation (MTF), has recently gained popularity for use in revision rhinoplasty or primary rhinoplasty when there is a paucity of autologous cartilage. However, there are currently no guidelines related to the use of intraoperative antibiotic soaking to reduce postoperative infection rates when using MTF FFCC. This study aimed to evaluate the efficacy of intraoperative antibiotic soaks in reducing surgical site infection rate when using MTF FFCC grafts in rhinoplasty. Methods: A retrospective chart review of patients who underwent rhinoplasty with the use of MTF FFCC in the senior author's practice was conducted between May 2017 and June 2022. The inclusion criteria were rhinoplasty cases using MTF FFCC with minimum of 12 months of follow-up. Fisher exact test was conducted to determine significance in rates of postoperative infection for patients who underwent rhinoplasty with the use of MTF FFCC with (1) intraoperative antibiotic solution soak versus (2) no antibiotic solution soak. Results: A total of 310 patients were included and separated into two cohorts, MTF FFCC intraoperative antibiotic solution soak (n = 200) and no antibiotic solution soak (n = 110). There were a total of four (1.3%) cases of infection, all in the antibiotic soak group. There was no statistically significant difference between the rate of infection in the two cohorts (P = 0.301). Conclusion: Our retrospective cohort study demonstrates that soaking MTF FFCC in an antibiotic solution intraoperatively does not reduce postoperative infection rates in rhinoplasty.

The Impact of L4-5 Minimally Invasive Transforaminal Lumbar Interbody Fusion on Two-year Adjacent-Level Parameters.

OBJECTIVE: This study evaluates the impact of L4-5 minimally invasive surgery (MIS)-TLIF on adjacent-level parameters. METHODS: This is a retrospective study performed on consecutive patients between January 2015-December 2019. The index- and adjacent-level segmental lordosis (SL) and disc angle (DA) were measured. Patient-reported outcomes (PROs) were collected preoperatively and at 3-24 months postoperatively. Factors influencing changes in adjacent-level parameters and the occurrence of adjacent segment degeneration (ASDeg) were assessed. RESULTS: One hundred and seventeen adult patients, averaging 65.5 years of age and slight preponderance of female (56.4%), were analyzed. L4-5 SL decreased at 2 years (p<0.05), but L4-5 DA significantly increased at all timepoints (p<0.05). While L3-4 SL and DA significantly decreased at all timepoints (p<0.05), L5-S1 SL decreased at 3 and 12 months (p<0.05) and L5-S1 DA only significantly decreased at 2 years (p<0.05). All PROs improved significantly (p<0.0001). The ASDeg rate was 19.7% at 2.2 years. Cephalad and caudal ASDeg rates were 12.0% and 10.3%, respectively. Eight patients (6.8%) required adjacent-level reoperations, mainly at L3-4 (6 cases). The use of expandable cage significantly reduced the odds of caudal ASDeg (OR 0.15, p=0.037), but had no significant effect on cephalad ASDeg.. CONCLUSIONS: L4-5 MIS-TLIF had a more consistent effect on L3-4 than L5-S1. Although adjacent-level SL and DA decreased over time, their association with ASDeg appears limited, suggesting a multifactorial etiology. L4-5 MIS-TLIF provides demonstrable clinical benefits with lasting PRO improvements and low adjacent-level reoperations.

Interorganelle phospholipid communication, a house not so divided.

The presence of membrane-bound organelles with specific functions is one of the main hallmarks of eukaryotic cells. Organelle membranes are composed of specific lipids that govern their function and interorganelle communication. Discoveries in cell biology using imaging and omic technologies have revealed the mechanisms that drive membrane remodeling, organelle contact sites, and metabolite exchange. The interplay between multiple organelles and their interdependence is emerging as the next frontier for discovery using 3D reconstruction of volume electron microscopy (vEM) datasets. We discuss recent findings on the links between organelles that underlie common functions and cellular pathways. Specifically, we focus on the metabolism of ether glycerophospholipids that mediate organelle dynamics and their communication with each other, and the new imaging techniques that are powering these discoveries.

Accuracy of a Single-Lead ECG Device for Diagnosis of Cardiac Arrhythmias Compared Against Cardiac Electrophysiology Study.

BACKGROUND: Single-lead electrocardiogram (ECG) devices may allow detection and diagnosis of cardiac rhythms. However, data on their accuracy for detecting cardiac arrhythmias beyond atrial fibrillation are limited. We aimed to determine the accuracy of the AliveCor KardiaMobile (AC) (AliveCor Inc, Mountain View, CA, USA) for the diagnosis of arrhythmias against gold standard cardiac electrophysiology study (EPS). METHOD: Patients undergoing clinically indicated EPS underwent simultaneous rhythm recording with an AC, standard 12-lead ECG, and EP catheters for intracardiac electrograms. Rhythms recorded during EPS were classified based on electrogram, 12-lead ECG, and clinical findings. Blinded reviewers provided differential diagnoses for the single-lead AC tracings; a separate reviewer compared diagnoses made between the AC tracings and EPS findings. RESULTS: In 49 patients, 843 cardiac rhythms were captured during 502 AC recordings. Analysis of tracings containing sinus rhythm (n=273) returned an overall accuracy of 92%, with sensitivity and specificity values of 93% and 92%, respectively. Accuracy for tracings per rhythm was atrial fibrillation 91% (n=51); supraventricular tachycardia accuracy was 89% (n=191), ventricular tachycardia 91% (n=198), ventricular fibrillation 98% (n=11), and asystole 100% (n=5). Accuracy for supraventricular ectopy was 93% (n=28) and for premature ventricular complexes was 91% (n=86). Overall accuracy was 94% for solitary rhythms and 93% in tracings from patients with baseline bundle branch block. CONCLUSIONS: When compared against the gold standard EPS diagnosis, the interpretation of arrhythmias recorded by an AliveCor single-lead ECG device had reasonable diagnostic accuracy.

Work-Related Musculoskeletal Disorders in Endoscopic Sinus and Skull Base Surgery: A Systematic Review With Meta-analysis.

OBJECTIVE: Endoscopic sinus and skull base surgery has led to significant improvements in patient outcomes, yet may have come at a cost to surgeons' musculoskeletal (MSK) health. We aimed to determine the prevalence and characteristics of work-related MSK disorders (WRMDs) in endoscopic sinus and skull base surgeons; to investigate contributing factors for WRMD in this population; and to evaluate the effectiveness of ergonomic interventions on the severity or prevalence of WRMD in this population. DATA SOURCES: Medline, Embase, CINAHL, Web of Science, and Scopus from inception to April 2, 2024. A bibliographic examination was performed for further papers. REVIEW METHODS: Inclusion criteria included original peer-reviewed papers with work-related MSK outcomes (prevalence, contributing factors, and interventions) relating to endoscopic sinus and/or skull base surgeons in any language. RESULTS: Of 25,772 unique citations, 37 studies met the inclusion criteria. The pooled lifetime, point, and 12-month prevalences of WRMD were 75.9% (95% confidence interval; I2, 67.2%-83.6%, I2 95.6%), 80.8% (77.0%-84.3%, I2 98.0%), and 82.0% (71.8%-90.3%, I2 60.96%) respectively. The neck, lumbar spine, and thoracic spine were the most commonly involved areas. One of 9 studies on contributing factors investigated discomfort as an outcome. The remainder focussed on surrogate outcomes (eg, posture, hand dysfunction). Two of the 13 intervention studies investigated pain or fatigue as an outcome. The remainder targeted posture, muscle activity, or workload. CONCLUSION: WRMDs are highly prevalent in endoscopic sinus and skull base surgeons. Further studies focusing on the direct outcomes of WRMD such as pain are needed.

Effects of Screen-Based Leisure Time on 24 Subsequent Health and Wellbeing Outcomes: A Longitudinal Outcome-Wide Analysis.

BACKGROUND: Previous research has shown that screen-based leisure time is related to physical and mental health, relationships, and prosocial behaviors. However, it remains unclear whether screen-based leisure time causally affects wellbeing, as previous studies have relied on cross-sectional data, focused on one type of media use (e.g., social media, video games, or internet), or assessed a narrow set of outcomes. METHOD: We used three waves (2016, 2017, 2019) of national longitudinal data from the New Zealand Attitudes and Values Study to investigate the effects of screen-based leisure time on 24 parameters of wellbeing (n = 11,085). We operationalized screen-based leisure as the sum of time spent browsing the internet, using social media, watching/reading the news, watching videos, and playing video games. We followed the outcome-wide analytic design for observational data by performing a series of multivariable regression models estimating the effect of screen-based leisure time on 24 wellbeing outcomes and assessed potential unmeasured confounding using sensitivity analyses. RESULTS: In our primary analysis with the total sample, total screen-based leisure time was associated with a very modest decrease in body satisfaction and a very modest increase in body mass index. Possible evidence of associations was found with increases in number of hours spent exercising and volunteering each week, as well as decreases in number of average daily hours of sleep, self-control, and subjective health. CONCLUSION: Screen-based leisure time has the potential to affect health and wellbeing. Results are discussed in light of the high prevalence of screen-based leisure time.

Mastoid Fascia Tissue Graft as a Tip Camouflage Technique in Rhinoplasty: A Reliable Alternative to Soft Cartilage Grafts.

BACKGROUND: Traditional rhinoplasty tip grafts often lead to visibility issues, prompting patients to seek revision surgery. The mastoid fascia tissue graft (MFTG) provides a natural-looking alternative with an acceptable risk of complication. MFTG remains less visible through the skin and helps camouflage and conceal tip irregularities. This study of 193 patients examines MFTG's effectiveness in nasal tip refinement, evaluating revision and infection rates. METHODS: A retrospective analysis of MFTG use for nasal tip aesthetics during open rhinoplasty in the senior author's practice was conducted from January 2019 to June 2022. Inclusion criteria encompassed open rhinoplasty cases using mastoid tissue for tip aesthetics with at least 12 months of follow-up. Among 2003 cases, 193 met these criteria and were evaluated for subsequent revision and infection rates. RESULTS: The average patient age was 34.2 years (175 females, 18 males). Primary rhinoplasties were done on 113 patients, with 80 receiving revision surgeries. Average follow-up was 14.8 months. 6 (3.1%) patients overall needed extended antibiotics, including 1 (0.9%) primary rhinoplasty and 5 (6.3%) secondary rhinoplasty patients. Overall, 6 (3.1%) patients required revision rhinoplasty, comprising of 1 (0.9%) primary and 5 (6.3%) secondary rhinoplasty patients. CONCLUSIONS: MFTG use for nasal tip aesthetics is a safe, convenient, and effective technique in camouflaging and concealing nasal tip contour irregularities in both primary and revision rhinoplasty. Use of MTFG is associated with minimal morbidity.

Human plasma cells engineered to secrete bispecifics drive effective in vivo leukemia killing.

Bispecific antibodies are an important tool for the management and treatment of acute leukemias. As a next step toward clinical translation of engineered plasma cells, we describe approaches for secretion of bispecific antibodies by human plasma cells. We show that human plasma cells expressing either fragment crystallizable domain-deficient anti-CD19 × anti-CD3 (blinatumomab) or anti-CD33 × anti-CD3 bispecific antibodies mediate T cell activation and direct T cell killing of B acute lymphoblastic leukemia or acute myeloid leukemia cell lines in vitro. We demonstrate that knockout of the self-expressed antigen, CD19, boosts anti-CD19-bispecific secretion by plasma cells and prevents self-targeting. Plasma cells secreting anti-CD19-bispecific antibodies elicited in vivo control of acute lymphoblastic leukemia patient-derived xenografts in immunodeficient mice co-engrafted with autologous T cells. In these studies, we found that leukemic control elicited by engineered plasma cells was similar to CD19-targeted chimeric antigen receptor-expressing T cells. Finally, the steady-state concentration of anti-CD19 bispecifics in serum 1 month after cell delivery and tumor eradication was comparable with that observed in patients treated with a steady-state infusion of blinatumomab. These findings support further development of ePCs for use as a durable delivery system for the treatment of acute leukemias, and potentially other cancers.